Yanli Song

Gene expression levels of cytokines in peripheral blood mononuclear cells from patients with pulmonary embolism.

The aim of this study was to investigate the differential gene expression of cytokines in peripheral blood mononuclear cells (PBMCs) from patients with pulmonary embolism (PE) and controls. Twenty patients with PE and twenty control patients matched for gender and age with the PE group were recruited into the study. Human cDNA microarray analysis was used to detect differences in the expression of cytokine-associated genes between the two groups. In PE patients, the expression levels of the genes encoding IFNα5, IFNα6, IFNα8, IFNα14, IFNκ, IFNω1, IFNε1 and IFNγ were significantly lower compared with controls (P<0.05). The expression levels of the genes encoding IL1α, IL2, IL3, IL9, IL13, IL17β, IL19, IL22, IL23α, IL24, IL25 and IL31 were significantly lower (P<0.05), while IL10 and IL28A mRNA expression levels were higher in PE patients compared with controls (P<0.05). In PE patients, Cxcl1, Cxcl2, Cxcl6, Cxcl13 and Cxcl14 mRNAs were significantly upregulated (P<0.05), however, Cxcl10 mRNA was significantly downregulated (P<0.01). In PE patients, the mRNA expression levels of TNF superfamily members 1, 9 and 13, and TNF receptor superfamily members 1A, 1B, 9, 10B, 10C, 10D and 19L, were significantly upregulated (P<0.05), whereas TNF receptor superfamily members 11B, 19 and 25 were significantly downregulated compared with controls (P<0.05). The mRNA expression levels of granulocyte-macrophage colony‑stimulating factor, granulocyte colony-stimulating factor, erythropoietin, thrombopoietin and mast cell growth factor were significantly lower in PE patients compared with controls (P<0.05). In PE patients, the mRNA expression levels of a variety of cytokines were imbalanced and cellular immune function was downregulated compared with controls. Thus, PE patients may be more susceptible to infections caused by viruses, intracellular bacteria and parasites.

Symptomatic Venous Thromboembolism Is a Disease Related to Infection and Immune Dysfunction

The characteristics of human genomics and cellular immune function between clinically symptomatic venous thromboembolism (VTE) and controls were systematically compared to explore the immunologic pathogenesis of VTE. Microarray assay showed the mRNA expressions of genes related to non-specific cellarer immune and cytokines were significantly down-regulated. Abnormal expressions of CD3+, CD4+, CD8+, NK marker CD16+56+, CD19 and aberrant CD4+/CD8+ ratio were detected in 54 among 56 patients. In PE patients, microarray assay revealed the imbalance in the expressions of genes related to the immune system. The expressions of genes related to non-specific immune cells and cytokines were markedly up-regulated and those associated with cellular immune were dramatically down-regulated. In VTE patients, cytological examination indicated the functions of NK cells were significantly compromised, and the antigen recognition and killing function of T cells markedly decreased. The consistence between genomic and cytological examination suggests the symptomatic VTE is closely associated with the infection and immune dysfunction.

Expression of B-cell-associated genes in peripheral blood mononuclear cells of patients with symptomatic pulmonary embolism

The aim of the present study was to identify differentially expressed B‑cell‑associated genes in peripheral blood mononuclear cells and investigate the gene expression characteristics of the different stages of B‑cell activation. A total of 20 patients with pulmonary embolisms (PE) and 20 age‑ and gender‑matched controls were enrolled in the present study. Human complementary DNA microarray analysis was used in order to detect the differential expression of B‑cell‑associated genes between the PE and control groups. Messenger (m)RNA expression was detected for 82 genes involved in B‑cell activation. The results showed that PE patients exhibited significantly increased expression levels of the B‑cell receptor genes LYN, CD22, SYK, BTK, PTPRC and NFAM1, whereas expression levels of FYN, FCRL4 and LAX1 were significantly decreased compared to those of the control group. Expression levels of T‑cell‑dependent B‑cell‑activation genes, including EMR2, TNFSF9, CD86, ICOSLG, CD37 and CD97, were significantly upregulated in PE patients, whereas SPN mRNA expression was significantly downregulated compared with those of the control group. LILRA1 and TLR9 T cell‑independent B‑cell activation mRNAs were significantly upregulated in PE patients compared with those of the control group. In addition, the expression levels of B‑cell‑activation regulator genes, including CR1, LILRB4 and VAV1, were significantly increased, whereas SLAMF7 expression levels were significantly decreased in PE patients compared with those of the control group. Furthermore, the expression levels of B‑cell‑activation‑associated cytokine genes demonstrated a significant upregulation of LTA and IL10 and downregulation of L1A, IFNA5, IFNA6, IFNA8, IFNA14, IL2, IL13 and IFNG in PE patients compared to those of the control group. In conclusion, the differential gene expression at different stages of B‑cell activation between healthy controls and PE patients indicated that B‑cell function was reduced or disorganized in patients with symptomatic PE.

Characteristics of the complement system gene expression deficiency in patients with symptomatic pulmonary embolism

Abstract Introduction Pulmonary embolism (PE) is a disease with a high mortality and morbidity rate, and the pathogenesis of PE remains still unclear. We aimed to investigate the gene expression differences of the complement system in peripheral blood mononuclear cells (PBMCs) from patients with symptomatic PE and controls. Methods Twenty cases of PE patients and twenty sex and age matched controls were recruited into the study. Human cDNA microarray analysis was used to detect the gene expression difference of the complement system between the two groups. Results 1). Expression of twenty-one genes encoding complement components was detected. In PE patients, expression of the genes encoding C1qα, C1qβ, C4b, C5 and Factor P was significantly greater (P<0.05) than controls, while C6, C7, C9, mannose-binding lectin (MBL) and mannan-binding lectin serine peptidase 1 (MASP1) mRNAs were lower (P<0.05) than controls. 2). Expression of seven genes encoding complement receptors was examined. In PE patients, CR1, integrin αM, integrin αX and C5aR mRNAs were significantly up-regulated (P<0.01) compared with controls. 3). Seven genes encoding complement regulators were examined. The mRNA expression of CD59 and CD55 was significantly up-regulated (P<0.05), whereas Factor I mRNA was significantly down-regulated (P<0.05) in PE patients than controls. Conclusions In PE patients, the mRNA expressions of complement components, receptors and regulators were unbalanced, suggesting dysfunction and/or deficiency of the complement system, which leads to decreased function of MAC-induced cell lysis in PE patients finally.

Analysis on the pathogenesis of symptomatic pulmonary embolism with human genomics.

BACKGROUND: In the present study, the whole human genome oligo microarray was employed to investigate the gene expression profile in symptomatic pulmonary embolism (PE). METHODS: Twenty patients with PE and 20 age and gender matched patients without PE as controls were enrolled into the present study in the same period. The diagnosis of PE was based on the clinical manifestations and findings on imaging examinations. Acute arterial and/or venous thrombosis was excluded in controls. The whole human genome oligo microarray was employed for detection. Statistical analysis was performed with t test following analysis of very small samples of repeated measurements and Gene Ontology (GO) analysis. RESULTS: Genomic data showed no damage to vascular endothelial cells in PE patients. Genomic data only found increased mRNA expression of a small amount of coagulation factors in PE patients. In the PE group, anticoagulant proteins, Fibrinolytic system and proteins related to platelet functions only played partial roles in the pathogenesis of PE. In addition, the mRNA expressions of a fraction of adhesion molecules were markedly up-regulated. Gene Ontology analysis showed the genes with down-regulated expressions mainly explain the compromised T cell immunity. Symptomatic VTE patients have compromised T cell immunity. CONCLUSION: The damage to vascular endothelial cells is not necessary in the pathogenesis of VTE, and only a fraction of factors involved in the shared coagulation cascade are activated. Genomic results may provide a new clue for clinical diagnosis, treatment and prevention of VTE.

Immune Cell Repertoire and Their Mediators in Patients with Acute Myocardial Infarction or Stable Angina Pectoris

Background: To evaluate the natural innate and adaptive immunity through gene expression and cytology levels in peripheral blood mononuclear cells in patients with acute myocardial infarction (AMI), stable angina pectoris (SAP) and controls. Methods: 210 patients with AMI, 210 with SAP, and 250 clinical controls were recruited. Whole human genome microarray analysis was performed in 20 randomly chosen subjects per group were examined to detect the expressions of complement markers, natural killer cells, T cells and B cells. The quantity of these cells and related cytokines as well as immunoglobulin levels were measured in all subjects. Results: In AMI group, the mRNA expressions of late complement component, markers of natural killer cells, CD3+, CD8+ T cells and B cells were down-regulated, while those of early complement component and CD4+T cells were up-regulated (p<0.05). In both AMI and SAP patients, the quantity of natural killer cells, CD3+, CD8+ T cells, B cells, IgM and IgG were significantly lower than those of the controls. CD4+ T cells, CH50, C3, C4, IL-2, IL-4, IL-6 and IFN-γ were significantly higher (p<0.05). Conclusions: In AMI patients, both of gene expressions related to complement, natural killer cells, CD3+, CD8+ T cells, B cells and the quantity of these immune cells decreased while cell number reduced in SAP patients. Immune function in both AMI and SAP patients decreased especially in AMI patients with declined gene and protein levels. To improve the immune system is a potential target for medical interventions and prevention in AMI.

Increased Expressions of Integrin Subunit β1, β2 and β3 in Patients with Acute Infection

Objective: Our previous studies have shown that integrin subunits β1, β2 and β3 were the core proteins of venous thrombi and potential useful biomarker of venous thromboembolism (VTE). Patients with acute infection have a high risk of VTE. In this study we explored that is there any relevance between core proteins and acute infection. Methods: A total of 230 patients (112 females) with clinically proven acute infection in the emergency unit were recruited into this study, meanwhile 230 patients without acute infection matched in sex and age were recruited as control group. Flow cytometry was done to measure the expressions of blood integrin β1, β2, β3 and cellular immunity (CD3, CD4, CD8, CD4/CD8, CD16CD56 and CD19). The association degree between increased core proteins and acute infection was analyzed by calculating the relative risk (RR). Results: The expression of integrin β1, β2 and β3 was markedly increased in patients with acute infection (P=0.000, 0.000 and 0.015, respectively). The relative risk ratio (RR) of increased integrin β1, β2 and β3 in acute infection patients was 1.424 (95%CI: 1.156-1.755, P=0.001), 1.535 (95%CI: 1.263-1.865, P=0.000) and 1.20 (95%CI: 0.947-1.521, P=0.148), respectively. Combined integrin β1, β2 and β3 analysis showed that the relative risk ratio (RR) of increased in patients with acute infection was 2.962 (95%CI: 1.621-5.410, P=0.001), and this relative risk (RR) rise to 3.176 (95%CI: 1.730-5.829, P=0.000) in patients with respiratory tract infection (RTI). Conclusion: As the core proteins of venous thrombi, integrinβ1, β2 and β3 were markedly increased expression in patients with acute infection, which maybe explain the increased risk of VTE in acute infection patients. A weakened immune system could be the basic condition of VTE occurrence.